Living Related Kidney Transplantation in Libya: A Single Center Experience

Living Related Kidney Transplantation in Libya: A Single Center Experience A. Usta, T. Shawish, A. Mishra, E.F. Ehtuish, H. Ajaj, N. Milud, A. Shebani, T. Abdulmola, and U. Tejori ABSTRACT Objective. The aim of this study was to establish a successful living related kidney transplantation program in Libya and to bring down health care costs in management of patients with end-stage renal disease. Patients and Methods. Since the transplantation program was launched on August 17, 2004, 135 patients have been transplanted up to August 17, 2007. The donors and recipients were screened prior to transplantation. Our immunosuppressive protocol was cyclosporinebased. Both donors and recipients were followed in the transplant outpatient clinic. Results. Among 135 accepted pairs, 133 cases (98.5%) were genetically related donors and recipients and 2 cases were emotionally related. Mean donor age was 37 ⫾ 9.5 years (range, 18 –56 years). Recipient age was significantly lower, namely, 37 ⫾ 13.6 years (range, 7– 67 years). Among the recipients, 95 (70.4%) were males and 40 (29.6%) females, while among the donors, 102 (75.6%) were males and 33 (24.4%) females. The most common donor-recipient relationship was brother-to-brother. There was no early or late surgical mortality among donors. Delayed graft function was observed in 3 patients (2.2%), acute rejection in 6 (4.4%), and posttransplantation infections in 8 (5.9%). Urinary tract infections were diagnosed in 6 patients (4.4%) and pneumonia in 3 (2.2%). Postsurgical complications included ureteric kink in 2 patients (1.5%) and an anastomotic urine leak in 4 (3.0%). At 36 months, graft survival was observed in 130 patients (96.3%) and patient survival in 126 (93.3%). Conclusion. The Libyan National Organ Transplant Program has been successful with results comparable to international levels.

K

IDNEY TRANSPLANTATION remains the optimal therapy for patients with end-stage renal failure. Kidney transplantation is not only associated with an improved quality of life compared with all other renal replacement therapies, but also offers a significantly extended life span. Realistically, only living donor transplantation offers the option of sparing the recipient a long waiting period on dialysis. Kidney transplantation and immunosuppressive therapy are associated with increased risks for certain types of infections, an increased tumor incidence, and an increased risk for cardiovascular complications. To address these problems, specific recommendations for patient surveillance have been provided by various transplantation societies. There are approximately 2100 patients presently on dialysis in Libya. New cases of end-stage renal disease show an incidence of 80 to 100/million/year in Libya. The Libyan National Organ Transplant Program completed its

third year since inception in August 2004, during which time 135 patients have been transplanted from living related donors. Our immunosuppressive protocols are cyclosporinebased with steroids only for the first month posttransplantation. Although we have succeeded in establishing the regulation that promotes deceased donation and although we have also commenced an organ donation education program for society, deceased donation still seems far away. Herein we have presented our entire living donor experience. From the Departments of Surgery (A.U., T.S., E.F.E., T.A.), Nephrology (A.S.), Radiology (A.M.), and Anaesthesia (H.A., N.M.), National Organ Transplant Program, Tripoli Central Hospital, Tripoli, Libyan Arab Jamahirriya. Address reprint requests to Prof Ehtuish F. Ehtuish, National Organ Transplant Program, PO Box 84536, Tripoli Central Hospital, Tripoli, Libya. E-mail: [email protected]

0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.06.063

© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710

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Transplantation Proceedings, 40, 3428 –3433 (2008)

LIVING RELATED KIDNEY TRANSPLANTATION: LIBYA

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PATIENTS AND METHODS Selection Procedure Potential donors and recipients were first informed by the medical team (without any pressure or obligation) about the risks and benefits of the living donor transplantation procedure. Prerequisites for further evaluation were blood group compatibility and a negative cross-match. Subsequently, potential donors underwent an extensive medical examination. Kidney function was measured by means of the serum creatinine, 24-hour urine collection for creatinine clearance, and estimation of proteinuria as well as urinalysis. In the event of proteinuria and/or microscopic hematuria, donation was excluded. All donors and recipients underwent screening for hepatitis B and C. All donors also underwent a routine ultrasound examination to exclude congenital renal anomalies. Computed tomographic angiography was performed as one of the last examinations to determine the vascular and ureteric anatomy.

Transplantation Procedure Donors in whom the renal angiogram did not show any vessel abnormality and/or kidney malfunction underwent left nephrectomy. In other subjects with vascular anomalies/complex anatomy, we performed a right nephrectomy. Left-to-right or right-to-left transplantation was performed routinely with other combinations when necessary. Living kidney donation and transplantation were performed exclusively by the most experienced surgeon. Donor and recipient were prepared in parallel operating rooms. Usually the incision for transplantation was not started until the kidney was ready to be removed. We recorded warm and cold ischemia times. The renal artery anastomosis was performed end-to-end to the internal iliac artery or end-to-side to the external iliac artery. The renal vein was anastomosed end-to-side to the external iliac vein. A neoureterocystostomy was performed.

Postnephrectomy Donor Follow-up All donors were monitored closely for 4 to 6 days and thereafter discharged for outpatient follow-up.

Recipient Management and Outcome Immunosuppression for HLA-identical patients included steroids, cyclosporine, and mycophenolate mofetil (MMF) or Myfortic versus quadruple therapy including induction immunosuppression with Simulect (Novartis Pharma, Numberg, Germany) in nonidentical patients.

We presented cytomegalovirus (CMV) prophylaxis for all patients who tested IgG positive or if the donor was IgG positive; patients were regularly screened for CMV IgM and IgG antibodies. At the occurrence of clinical signs of rejection, a renal biopsy was performed. Initial treatment included steroids (Solumedrol 500 mg for 3 days). In cases of steroid-resistant rejection, ATG (Fresenius S, Fresenius Hemocare, Gräfelfing, Germany) was prescribed for 2 weeks. Delayed graft function (DGF) was defined as a postoperative requirement for dialysis, even in cases in which only 1 dialysis was necessary. Recipients were compared for incidence of DGF, number/type of histologically proven rejections, rejection treatment, infectious, surgical, or medical complications, as well as kidney function measured by serum creatinine. The regimen followed at our center was: methylprednisolone (MP) 500 mg (IV) intraoperatively followed by a dose of 250 mg (IV) q 24 h on postoperative day (POD) 1; 125 mg q 24 h on POD 2; 80 mg (IV) q 24 h on POD 3; oral prednisolone replaced MP on POD 4 to 40 mg/d and POD 5 to 20 mg/d. The dose was tapered to 10 mg on POD 11 and steroids were stopped on POD 29. MMF (1 g twice daily) was recently replaced with Myfortic (720 mg twice daily). Cyclosporine was withheld until the serum creatinine dropped to ⬍2.5 mg usually on POD 1 to 3 and initiated at a dose of 6 to 8 mg/kg/d. The regimen for maintenance therapy was: cyclosporine (3–5 mg/kg/d) adjusted to 150 to 250 ng/mL. MMF (1 g twice daily) was recently changed to Myfortic (720 mg twice daily). Cyclosporine was monitored and kept in the C0 range 150 to 250 ng/mL.

Statistics The results were analyzed for significance which was accepted for P ⬍ .05. Results are expressed as mean values ⫾ standard deviations. The Student t test was used to compare donor and recipient characteristics before and after transplantation.

RESULTS Selection Procedure

One hundred thirty-five living related kidney transplantations were performed between August 17, 2004 and August 17, 2007. There was some decline in the number of transplantations in the second year (Fig 1). We observed a monthly fluctuation in the number of patients transplanted according to the availability of willing and surgically fit donors (Fig 2). Among 140 pairs presenting for living donor

48 47 46 45 44 Progress of work in LNOTP

43 42 41 40 39 2004-05

2005-06

2006-07

Fig 1. Progress of work in the Libyan National Organ Transplant Program (LNOTP) over the 3-year period.

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USTA, SHAWISH, MISHRA ET AL 17 Aug'04-17 Aug.'05

18 Aug.'05 - 17`Aug.'06

18 Aug.'06 - 17 Aug.'07

10 9 8 7 6 5 4 3 2 1

transplantation, 5 (3%) were not accepted, the main reason being medical problems in the donor (n ⫽ 4) or extensive atherosclerosis of the recipient’s iliac vessels (n ⫽ 1). Among the 135 accepted pairs, 133 donor/recipient pairs were living related (98.5%) and emotionally related in 2 cases (1.5%). Mean donor age was 37 ⫾ 9.5 years (range, 18 –56 years). Recipient age was lower, namely, 37 ⫾ 13.6 years (range, 7– 67 years). Among 135 recipients, 95 (70.4%) were males and 40 (29.6%) females. Among the 135 donors, 102 (75.6%) were males and 33 (24.4%) females. The patients had come from all corners of the country with the majority from the largest 2 cities, Tripoli and Benghazi (Fig 3). The most common donor-recipient rela-

t us

ly

Au g

17

Ju

ne Ju

ay M

Ap r

h ar c M

Au g Se ust pt em be r O ct ob er N ov em be r D ec em be r Ja nu ar y Fe br ua ry

17

Fig 2. Monthly trend in kidney transplantations.

il

0 -1

tionship was between siblings followed by son-to-parent (Fig 4). The most common blood groups in both donors and recipients were either O or A. The HLA matching was either identical or 1 haplotype. The most common causes of end-stage renal disease were glomerulonephritis or hypertension in 70% of the patients. Among 135 patients, 81% were negative upon hepatitis screening. Postnephrectomy Follow-up

There was no early or late surgical mortality. There were no early complications after nephrectomy in any donor. Operative site collection was the only late complication seen in 7 patients (5%), which was treated by antibiotics and drainTripoli

30

Sebha Tajora Tarhona Zawia

25

Jmail Benghazi Tobrouk

20

Marj SoqElkhamis Tmessa Teeji

15

QasrKhiar QasrBinGhashir Alzahra AljabalAlgharbi

10

AlBaida AlAsaaba Ejdabia Misrata

5

Yefren Gheryan AlGubba Murzug

0

Rujban Sirt

Fig 3. The patient distribution in Libya.

LIVING RELATED KIDNEY TRANSPLANTATION: LIBYA

40 35 30 25 No.

20 15 10 5 0 Br to Br

Br to Sr

Sr to Sr

Sr to Br

So So Mr Fr Fr to to to to to Fr Mr So So Dr

Mr to Dr

Dr to Fr

Dr H to Wto Ne to W H to Mr Un

Relationship

Fig 4. Relationship between donors and recipients. Br, brother; Sr, sister; So, son; Fr, father; Mr, mother; Dr, daughter; H, husband; W, wife; Ne, niece; Un, uncle.

age. None of the donors had an increase in serum creatinine or arterial blood pressure after donation. Recipient Management and Outcome

The immunosuppressive protocol at our center varied according to the immunological risk status and HLA tissue typing. HLA-identical recipients required no induction therapy, while non-HLA-identical subjects underwent induction with basiliximab (Simulect) at 20 mg on days 0 and 4. Early steroid withdrawal was applied to all recipients, except 3 patients (2.2%) who had Goodpasture’s syndrome (n ⫽ 1) and systemic lupus erythematosus (n ⫽ 2), who were maintained on small dose of steroids. All 3 patients with hypertension who underwent simultaneous unilateral or bilateral native nephrectomy show functioning grafts with normal blood pressure. The 3 pediatric patients (ages 7, 8, and 9 years) who received the kidney transplants from their mother, sister, and father, respectively, have excellent renal function and are back to school. DGF was observed in 3 patients (2.2%) who required dialysis for 2 to 3 weeks postoperatively. They all recovered completely with normal renal function. An acute rejection episode (ARE) was diagnosed and confirmed by biopsy in 6 patients (4.4%), who were treated with MP. Steroid-resistant cases required ATG. Complete graft recovery occurred in 4 of them, while graft loss was evident in 1 and the other remained with mild renal impairment. Posttransplantation infections were observed in 8 patients (5.9%), 1 of whom died due to infection and uncontrolled arterial bleeding. Urinary tract infection was diagnosed in 6 patients (4.4%) and pneumonia in 3 (2.2%). All patients recovered completely from their infections after antibiotic therapy. Postsurgical complications included ureteric kink which needed surgical reintervention in 2 (1.5%) of our early cases. An anastomotic urine leak needed

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surgical reintervention in 2 patients (1.5%) and spontaneously resolved in 2 patients (1.5%). Vascular thromboembolic disease with loss of graft was seen in 1 patient (0.74%) with acute tubular necrosis in 1 patient. One patient died during surgical reintervention due to posttransplantation external iliac artery “pseudo-aneurysm.” Superadded graft site infection leading to patient loss was seen in 1 (0.74%) and graft loss in 1 patient (0.74%). By August 2007, 2 patients (1.5%) had died with a functioning graft after a major stroke. Graft survival at 36 months was observed in 130 patients (96.3%), while patient survival in the same period was 126 patients (93.3%), as 4 patient deaths occurred with normally functioning renal grafts. The duration of hospital stay for the donors was 4 to 6 days (mean, 4.5 days) and for recipients it was 8 to 24 days (mean, 14 days). Kidney function at the time of discharge was acceptable with serum creatinine values of 1.1 ⫾ 0.5 mg/dL. At the present time, all donors are in excellent health and back to their normal lives. DISCUSSION

The first successful kidney transplantations in humans were obtained from identical twin living donors.1,2 Although transplanted before the development of chemical immunosuppression, many of these identical twin grafts showed long-term survival. With recognition of the immunosuppressive effects of prednisone and azathioprine, the use of nontwin donors became possible.3,4 Considerable controversy soon followed as to whether it was ethical to use living donors for kidney transplantation.5– 8 Proponents of the use of living donors noted that the short- and long-term patient and graft survival rates were better after living vs cadaveric donor transplantations. Opponents worried that living donor nephrectomy was a major operation with potential risk to the donor; they believed that these risks did not justify the benefits to the recipient. The concern centered on possible donor morbidity/mortality in the early postoperative period as well as potential long-term complications after unilateral nephrectomy. More recently, living unrelated donors have been utilized at several centers in an attempt to provide renal transplantation to more patients, and this has sparked even more controversy and “commercialization.” Our program has always advocated the use of living donors. We recognized the risks to the donor but decided that a fully informed donor could choose whether to accept them. Some Nordic studies have confirmed that donors do live longer, due to the close follow-up program with early detection of disease and prompt treatment9. Kidney transplantation in Libya had been nonexistent prior to 1989 when a small transplantation program was started at Al Zahra Hospital in Tripoli, Libya. The transplant program had dismal outcomes; during the next 8 years, only 63 transplantations were performed, so the program was completely suspended in 1997.

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The National Organ Transplant Program in Libya was conceived in August 2004 with adoption of recent diagnostic and immunosuppressive protocols. The first kidney transplantation was performed on August 17, 2004, and to date, 135 kidney transplantations have been performed from living related donors. In the last decade, as a result of improvements in patient care, optimization of immunosuppressive protocols, and introduction of new immunosuppressive agents, outcomes for living donor recipients have markedly improved. The single prospective decision that most positively affects longterm outcomes continues to be the availability of a living donor transplant. The improved outcomes are due to a multitude of reasons. First, immunosuppressive protocols have improved. Not only are new agents available, but also there has been time to learn their judicious use. Consequently, the incidence of ARE has decreased markedly; graft loss due to ARE has become rare. Second, the importance of infection in general and of CMV infection in particular, has been recognized. Protocols have been developed to decrease the incidence of CMV infection with the use of prophylaxis when required, and for recipients developing infections, more effective treatment regimens have emerged. Third, recipients are not as sick when admitted for transplantation. Dialysis techniques have improved over time; the use of erythropoietin has allowed candidates to remain healthier. In addition, screening regimens for transplant candidates have improved. For example, we now recognize that cardiovascular disease was often responsible for early posttransplantation deaths in recipients with good renal function, a recognition that has led to more thorough screening (including angiography). Candidates whose evaluation uncovers treatable disease now undergo pretransplantation treatment, hence, patient survival rates have improved. During the last 3 years in Libya, the general attitude toward kidney transplantation from living donors has seen a considerable change with more families willingly coming forward for transplantation. Despite a slump in the total number of patients transplanted in 2005–2006, there has been a steady increase in the number of patients transplanted in 2006 –2007, showing signs of a further increase in the coming year. One important observation of our study was the accidental detection of unknown medical problems in the donors which surprised them because they believed themselves to be healthy. Our incidence of ARE was low (3.7%), which can be attributed to our immunosuppressive regimen of cyclosporine, MMF/Myfortic, and prednisolone. Kim et al10 in 1999 reported the clear benefit of MMF-based therapy to reduce the incidence of ARE after living donor renal transplantation. ARE was treated with prednisone and ATG, when needed. The incidences of DGF and vascular complications at our center were also low probably due to improved surgical techniques.

USTA, SHAWISH, MISHRA ET AL

Excellent patient and graft survivals were observed among our living kidney transplantations. When comparing results, differences in immunosuppressive therapies must be taken into consideration. The 1-year death-censored graft survival rates of groups using similar immunosuppressive protocols to ours have been reported as high as 92% to 100%.11 We used quadruple immunosuppression in 2 cases of genetically unrelated living kidney transplantation and similar to the nonidentical genetically related, it resulted in excellent short-term graft survival. In our series, there was a higher incidence of male compared with female subjects who were willing to be donors. The majority of the patients came from the 2 major cities in Libya, Tripoli and Benghazi. The biggest challenge in transplantation today is increasing the number of available organs. We realized that many patients with end-stage renal disease do not have a willing or suitable genetically related donor. Instead, some of them have the opportunity to receive a kidney from an unrelated donor who has clear emotional bonds with the patient and stong motivation. In 1997, Binet et al12 reported 46 emotionally related, living kidney donor transplantations, concluding that it gave the chance for prompt transplantation to patients with endstage renal disease who thereby experienced successful social rehabilitation and greater graft survival rates. The donors, mostly spouses, showed high motivation and their donations were based on love and altruism. Karakayali et al13 reported 81 living unrelated kidney transplantations from spouses, concluding that interspousal kidney transplantation is an important option with good clinical results enabling a husband or wife to receive the “gift of life” from each other. In 2006, Roozbeh et al14 attributed the high survival rate of spousal donors to their strong emotional support. The excellent graft and patient survival results were comparable to other transplant programs in the major centers of the world15 Celik et al16 in 2007 reported a case of successful reuse of a kidney graft with a 3-year follow-up. Various immunological, metabolic, and technical factors render pediatric recipients with end-stage renal disease unique from their adult counterparts. In our series of 135 patients, we transplanted 2 children with excellent results. In 2006, Sipzen et al17 reported renal transplantations in 83 pediatric patients, concluding that better outcomes may be obtained by strict adherence to precise surgical techniques, better immunosuppressive management, and early diagnosis/effective management of complications. Our results among living related transplantations were better than some reported literature series.18,19 In 3 patients with malignant hypertension, we performed unilateral nephrectomy and in 1 patient with polycystic kidney disease, bilateral nephrectomy. In 2007, Wagner et al20 developed an algorithm for performing bilateral nephrectomies for specific indications before or at renal transplantation in patients with polycystic kidney disease, concluding that concurrent bilateral nephrectomy was safe and did not compromise patient or graft outcomes.

LIVING RELATED KIDNEY TRANSPLANTATION: LIBYA

Besides undertaking living unrelated kidney transplantation to increase the donor pool, various other strategies have also been prescribed. Barry et al21 studied trends in kidney transplantation donor sources over a 15-year period, concluding the benefits of living donor renal transplants from genetically unrelated donors, of ABO-incompatible donors, and of cross-match positive donors as well as the improvements from the introduction of hand-assisted laparoscopic donor nephrectomy to increase the number of living renal donor transplants without compromising shortterm kidney transplant survival rates. According to the United Network for Organ Sharing (UNOS) Renal Transplant Registry report published in 2005,22 the number of nonspousal unrelated living donor transplantations has increased 10-fold over the 10 years and does not appear to be slowing. However, most authors agree that transplantation from living donors is a complementary, not substitutive, program to that from cadaveric donors, which should always be encouraged with awareness campaigns among the population and programs targeted to healthy personnel.23 The reluctance to use organs from living donors whose eligibility was previously considered marginal (eg, elderly donors) is declining throughout the world. At our center too, we have started to accept elderly donors ⬎50 years old to increase our pool. In 2007, Baid-Agrawal et al24 agreed that increased donor age should not be a hindrance to transplantation. However, thorough standardized evaluation and careful screening for premorbid conditions in both elderly donors and elderly recipients are essential. In our series, none of the donors developed end-stage renal disease postdonation. A few reports in the literature have observed a small incidence (0.5%) of this complication.25 We are following all of our donors with routine 6-monthly serum creatinine and urine analyses. In conclusion, the Libyan National Organ Transplant Program has based its clinical program on the most recent achievements in transplant medicine to optimize the outcome of kidney grafts and improve the quality of life of kidney transplant recipients. Although the transplantation community attempts to keep up with the increasing demand for transplantable organs, the supply continues to fall far short from the need. This observation prompted us to focus on the expansion of the available pool of deceased donor organs, besides emotionally related living donors. Because of excellent graft and patient outcomes in our series and low risks for donors, we advocate the use of living kidney donors. Kidney transplantation offers the greatest potential for return-to-normal renal function, increased longevity, improved quality of life, and lower health care costs.26 REFERENCES 1. Murray JE, Merrill JP, Harrison JH: Renal homotransplantation in identical twins. Surg Forum 6:432, 1955 2. Merrill JP, Murray JE, Harrison JH, et al: Successful homotransplantations of the human kidney between identical twins. JAMA 160:277, 1956

3433 3. Schwartz R, Dameshek W: The effects of 6-mercaptopurine on homograft reactions. J Clin Invest 39:952, 1960 4. Starzl TE, Marchioro TL, Porter KA, et al: The use of heterologous antilymphoid agents in canine renal and liver homotransplantation and in human renal homotransplantation. Surg Gynecol Obstet 124:301, 1967 5. Kries H: Why living donors should not be used whenever possible. Transplant Proc 17:1510, 1985 6. Woodruff MFA: Ethical problems in organ transplantation. Br Med J 1:1457, 1964 7. Starzl TE: Living donors: con. Transplant Proc 19:174, 1987 8. Spital A: Ethical and policy issues in altruistic living and cadaveric organ donation. Clin Transplant 11:77, 1997 9. Johnson EM, Anderson JK, Jacobs C, et al: Long-term follow-up of living kidney donors: quality of life after donation. Transplantation 67:717, 1999 10. Kim YS, Moon JI, Kim SI, et al: Clear benefit of mycophenolate mofetil based triple therapy in reducing the incidence of acute rejection after living donor renal transplantations. Transplantation 68:578, 1999 11. Humar A, Durand B, Gillingham K, et al: Living unrelated donors in kidney transplants: better long-term results than with non-HLA-identical living related donors? Transplantation 69:1942, 2000 12. Binet I, Bock AH, Vogelbach P, et al: Outcome in emotionally related living kidney donor transplantation. Nephrol Dial Transplant 12:1940, 1997 13. Karakayali F, Moray G, Colak T, et al: Results of kidney transplantation between spouses: a single-center experience. Transplant Proc 39:898, 2007 14. Roozbeh J, Mehdizadeh AR, Izadfar MA, et al: Comparison of spousal with other donor groups: study of a single center. Transplant Proc 38:562, 2006 15. Malek-Hosseini SA, Razmkon A, Mehdizadeh A, et al: Long term results of renal transplantation: a single-center analysis of 1200 transplants. Transplant Proc 38:454, 2006 16. Celik A, Saglam F, Cavdar C, et al: Successful reuse of a transplanted kidney: 3-year follow-up. Am J Kidney Dis 50:143, 2007 17. Sipzen H, Dalgic A, Karakayali H, et al: Renal transplantation in children. Transplant Proc 38:426, 2006 18. Rashed A, Aboud O: Renal transplantation: seventeen years of follow-up in Qatar. Transplant Proc 36:1835, 2004 19. Al-Jebory HM, Abd KH, Mahmood S, et al: Characteristics of kidney transplantation in Baghdad: an epidemiological study. Saudi J Kidney Dis Transpl 18:432, 2007 20. Wagner MD, Prather JC, Barry JM: Selective, concurrent bilateral nephrectomies at renal transplantation for autosomal dominant polycystic kidney disease. J Urol 177:2250, 2007 21. Barry JM, Conlin M, Golconda M, et al: Strategies to increase living donor kidney transplants. Urology 66(5 suppl):43, 2005 22. Cecka JM: The OPTN/UNOS Renal Transplant Registry. Clin Transpl 1, 2005 23. Pretagostini R, Rossi M, Iappelli M, et al: Survival in kidney transplantation from living donors: a single-center experience. Transplant Proc 36:467, 2004 24. Baid-Agrawal S, Frei UA: Living donor renal transplantation: recent developments and perspectives. Nat Clin Pract Nephrol 3:31, 2007 25. Fehrman-Ekholm I, Nordicn G, Lennerling A, et al: Incidence of end-stage renal disease among live kidney donors. Transplantation 82:1646, 2006 26. Jofne R, Lopez-Gomez JM, Moreno F, et al: Changes in quality of life after renal transplantation. Am J Kidney Dis 32:93, 1998